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Blood, 1 December 2006, Vol. 108, No. 12, pp. 3834-3842. Prepublished online as a Blood First Edition Paper on August 8, 2006; DOI 10.1182/blood-2006-04-010637. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-04-010637v1 108/12/3834    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Hryniewicz, A. Articles by Franchini, G. Search for Related Content PubMed PubMed Citation Articles by Hryniewicz, A. Articles by Franchini, G. Related Collections Gene Expression Immunobiology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY CTLA-4 blockade decreases TGF-, IDO, and viral RNA expression in tissues of SIVmac251-infected macaques Anna Hryniewicz, Adriano Boasso, Yvette Edghill-Smith, Monica Vaccari, Dietmar Fuchs, David Venzon, Janos Nacsa, Michael R. Betts, Wen-Po Tsai, Jean-Michel Heraud, Brigitte Beer, Diann Blanset, Claire Chougnet, Israel Lowy, Gene M. Shearer, and Genoveffa Franchini From the Animal Models and Retroviral Vaccines Section, Experimental Immunology Branch, and Biostatistics and Data Management Section, National Cancer Institute, Bethesda, MD; Department of General and Experimental Pathology, Medical University of Bialystok, Poland; Southern Research Institute, Frederick, MD; Division of Biological Chemistry, Biocentre, Innsbruck Medical University, Austria; Ludwig Boltzmann Institute of AIDS Research, Innsbruck, Austria; Department of Microbiology, University of Pennsylvania, Philadelphia; Medarex, Bloomsbury, NJ; and the Molecular Immunology Section, Children's Hospital Research Foundation, University of Cincinnati, OH. Regulatory T (Treg) cells are a subset of CD25+CD4+ T cells that constitutively express high levels of cytotoxic T lymphocyte antigen-4 (CTLA-4) and suppress T-cell activation and effector functions. Treg cells are increased in tissues of individuals infected with HIV-1 and macaques infected with simian immunodeficiency virus (SIVmac251). In HIV-1 infection, Treg cells could exert contrasting effects: they may limit viral replication by decreasing immune activation, or they may increase viral replication by suppressing virusspecific immune response. Thus, the outcome of blocking Treg function in HIV/SIV should be empirically tested. Here, we demonstrate that CD25+ T cells inhibit virus-specific T-cell responses in cultured T cells from blood and lymph nodes of SIV-infected macaques. We investigated the impact of CTLA-4 blockade using the anti–CTLA-4 human antibody MDX-010 in SIV-infected macaques treated with antiretroviral therapy (ART). CTLA-4 blockade decreased expression of the tryptophan-depleting enzyme IDO and the level of the suppressive cytokine transforming growth factor- (TGF-) in tissues. CTLA-4 blockade was associated with decreased viral RNA levels in lymph nodes and an increase in the effector function of both SIV-specific CD4+ and CD8+ T cells. Therefore, blunting Treg function in macaques infected with SIV did not have detrimental virologic effects and may provide a valuable approach to complement ART and therapeutic vaccination in the treatment of HIV-1 infection. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: HIV inhibits CD4+ T-cell proliferation by inducing indoleamine 2,3-dioxygenase in plasmacytoid dendritic cells Adriano Boasso, Jean-Philippe Herbeuval, Andrew W. Hardy, Stephanie A. Anderson, Matthew J. Dolan, Dietmar Fuchs, and Gene M. Shearer Blood 2007 109: 3351-3359. [Abstract] [Full Text] [PDF] This article has been cited by other articles: V. Cecchinato, E. Tryniszewska, Z. M. Ma, M. Vaccari, A. Boasso, W.-P. Tsai, C. Petrovas, D. Fuchs, J.-M. Heraud, D. Venzon, et al. Immune Activation Driven by CTLA-4 Blockade Augments Viral Replication at Mucosal Sites in Simian Immunodeficiency Virus Infection J. Immunol., April 15, 2008; 180(8): 5439 - 5447. [Abstract] [Full Text] [PDF] E. R. Van Gulck, G. Vanham, L. Heyndrickx, S. Coppens, K. Vereecken, D. Atkinson, E. Florence, I. Kint, Z. N. Berneman, and V. V. Tendeloo Efficient In Vitro Expansion of Human Immunodeficiency Virus (HIV)-Specific T-Cell Responses by gag mRNA-Electroporated Dendritic Cells from Treated and Untreated HIV Type 1-Infected Individuals J. Virol., April 1, 2008; 82(7): 3561 - 3573. [Abstract] [Full Text] [PDF] S. Li, E. J. Gowans, C. Chougnet, M. Plebanski, and U. Dittmer Natural Regulatory T Cells and Persistent Viral Infection J. Virol., January 1, 2008; 82(1): 21 - 30. [Full Text] [PDF] A. Boasso, M. Vaccari, A. Hryniewicz, D. Fuchs, J. Nacsa, V. Cecchinato, J. Andersson, G. Franchini, G. M. Shearer, and C. Chougnet Regulatory T-Cell Markers, Indoleamine 2,3-Dioxygenase, and Virus Levels in Spleen and Gut during Progressive Simian Immunodeficiency Virus Infection J. Virol., November 1, 2007; 81(21): 11593 - 11603. [Abstract] [Full Text] [PDF] L. E. Pereira, F. Villinger, N. Onlamoon, P. Bryan, A. Cardona, K. Pattanapanysat, K. Mori, S. Hagen, L. Picker, and A. A. Ansari Simian Immunodeficiency Virus (SIV) Infection Influences the Level and Function of Regulatory T Cells in SIV-Infected Rhesus Macaques but Not SIV-Infected Sooty Mangabeys J. Virol., May 1, 2007; 81(9): 4445 - 4456. [Abstract] [Full Text] [PDF] A. Boasso, J.-P. Herbeuval, A. W. Hardy, S. A. Anderson, M. J. Dolan, D. Fuchs, and G. M. Shearer HIV inhibits CD4+ T-cell proliferation by inducing indoleamine 2,3-dioxygenase in plasmacytoid dendritic cells Blood, April 15, 2007; 109(8): 3351 - 3359. [Abstract] [Full Text] [PDF] A. Hryniewicz, D. A. Price, M. Moniuszko, A. Boasso, Y. Edghill-Spano, S. M. West, D. Venzon, M. Vaccari, W.-P. Tsai, E. Tryniszewska, et al. Interleukin-15 but Not Interleukin-7 Abrogates Vaccine-Induced Decrease in Virus Level in Simian Immunodeficiency Virusmac251-Infected Macaques J. Immunol., March 15, 2007; 178(6): 3492 - 3504. [Abstract] [Full Text] [PDF]

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